Diabetes Update #10 Day 4, Monday June 13 from the American Diabetes Association National Meeting

Dr. Ruchi Mathur offers
perspectives of interest on topics from the American Diabetes Association's 65th
Annual Scientific Sessions (held in San Diego, California June 10-14, 2005)

Listen now to
Day 4, New Diabetes Compounds Similar to Byetta - Chasing the Lizards Tail! - from Dr. Ruchi Mathur who is at the diabetes conference in
San Diego
(MP3 3.30min 3.20MB)

This is Dr. Ruchi Mathur on the fourth day of the American Diabetes
Associations 65th annual meeting. This morning housed an extensive review of the
GLP-1 analog we discussed
earlier, known now as Byetta.

While the benefits and potential mechanisms were discussed in detail, one of
the problems that was reviewed is its short duration of action. In the body
GLP-1 is broken down by an enzyme called DPP-4. GLP-1 made by the body is broken
down in a matter of minutes. The new prescription GLP-1 product is altered, so
it lasts a few hours. However, it will still need to be injected at least twice
daily in most patients.

To overcome this problem, companies are working on two areas. The first is to
try to change the compound even more to make it longer acting. The second is to
try to inhibit DPP-4 from breaking down GLP-1. This session discussed ways in
which research in these two areas is proceeding.

Liraglutide and CJC-1131 are compounds currently being studied which are
similar to exenitide (Byetta) but have longer durations of actions. In a 5 week
study liraglutide was given to patients on no medication or on metformin
therapy, and compared to a group who continued on their prior regimen. After
adjusting the dose for about 3 weeks, patients were then continued for 5 weeks.
There was a decrease in fasting blood sugar levels in the group on liraglutide
and the side effect profile was similar to Byetta, with nausea in about 25%, and
withdrawal from the study in about 4%. CJC-1131 actually binds the protein
albumin in the blood, so it's life span is much longer. It likely will require
one shot every 1-2 days. When given to 81 patients on metformin, in 12 weeks the
A1c decreased from a baseline of about 7.9 by another 1.1%. Weight dropped about
5-6 pounds and the side effects were similar to Byetta.

There are a number of DPP-4 inhibitors being studied, with names such as
Vildagliptin, Saxagliptin and Sitagliptin. These agents basically inhibit 90% of
the action of DPP-4 and increase the life of GLP-1 in the body by about 3 times.
These agents have been tested alone and in combination with metformin, and in
general, they seem to reduce A1c by about 1% over 12 weeks. The weight reduction
is not as noticeable as with the GLP-1 analogs. These medications were safe and
tolerability in clinical trials.

So- what does this mean? Byetta is a break-though new treatment for type 2
diabetes. However, it does involve more than one injection a day. Longer acting
compounds with similar effects are being developed, and will likely be on the
market in a few years. Ways to inhibit the breakdown are also being studied.
These DPP-4 inhibitors have the advantage of being in a pill form, not a shot.
However, we may loose some of the intensity of the weight loss effect that is so
very appealing. You will no doubt be hearing more on these compounds in the
upcoming months. Read and hear the
next installment from the
conference.